The overarching goal of the Developmental Therapeutics (DT) Program is to develop and translate novel mechanism-driven anti-cancer therapeutics and therapeutic regimens. To accomplish this goal, DT Program members are engaged in highly collaborative anti-cancer therapeutics development efforts that aim to: 1) identify and develop novel therapeutics to target critical cancer cell signaling drivers; 2) develop novel therapeutics and therapeutic regimens to target hormone-driven cancers; 3) target and overcome therapeutic resistance; and 4) develop innovative preclinical models and facilitate rapid clinical translation. The DT Program research portfolio encompasses the development of trials targeting hormone refractory breast and prostate cancer ? cancers that are of particular importance for our WNY catchment area. The DT Program also has two other important missions. First, the DT Program, via the Early Phase Clinical Trials (EPCT) unit, functions as the conduit for bringing scientific findings from DT and other CCSG programs (in particular, CSBT, TII) to the clinic. EPCT provides an institution-wide resource for laboratory-based drug discoveries, preclinical efficacy studies, PK/PD modeling and pharmacometric studies, IND-enabling toxicology, IND submission support, and clinical trial conduct and management. Second, the DT Program is committed to training the next generation of basic and clinician scientists to develop expertise in all phases of drug development. The DT Program is co-led by Drs. Dean Tang, an expert on studying cancer stem cells and cancer cell heterogeneity, and Igor Puzanov, an expert on designing and executing clinical trials from pre-clinical phase through phase III with an emphasis on combining immune and targeted agents. This new Program leadership represents a strategic refocusing of DT's overall efforts in therapeutic development and rapid clinical translation, and has led to new initiatives, efforts, and program developments such as Program retreats, recruitment of Program Advisory members, regular bi-weekly DT seminar series, and new Program-focused funding mechanisms emphasizing on collaborations. The DT Program has 33 members from 10 departments. In the 2013-2017 funding cycle, DT Program members have demonstrated synergistic productivity in basic discovery and translational cancer research. The high impact of DT Program research is evidenced by: 1) the members' publications in top tier journals (total 893 publications and 74 in journals of JIF?10); 2) development of novel inhibitors and therapeutics to target `Achilles' heels' of cancer; and 3) innovative clinical trials. The DT Program has translated recent preclinical findings into 18 ongoing clinical trials led by DT members (7 of them Phase I) and 11 clinical trials performed in collaboration with other CCSG Programs (4 in Phase I). These clinical trials included 344 patients enrolled on treatment trials in CY2017 compared to 326 patients in 2012. Current annual peer-reviewed DT Program funding is ~$4.2M (direct cost), of which $3.0M is from NCI, and total research funding is $9.5M.